Dynamic Metabolite Profile Changes in Semen Ziziphi Spinosae During Ripening

ABSTRACT Rationale In traditional Chinese medicine, Semen Ziziphi Spinosae (SZS) is employed for alleviating conditions such as neurasthenia, sleep disorders, and anxiety. Its therapeutic effects are attributed to an abundance of biologically active compounds. The main objective of this study was the comparative profiling of SZS from different harvest times using a widely targeted metabolomics approach. Methods First, UPLC‐Q Trap‐MS/MS was used for identification of metabolic profile. Then, multivariate statistical analysis and KEGG enrichment analysis were performed to screen out the differential metabolites and related metabolic pathways among different growth stages. Results In total, 466 metabolites were identified at three different growth and development stages (T1, T2, and T3) of SZS using UPLC‐Q Trap‐MS/MS, including 83 flavonoids, 80 phenolic acids, 67 amino acids and derivatives, 56 lipids, 39 nucleotides and derivatives, 38 organic acids, 1 quinone, 6 lignans and coumarins, 53 other metabolites, 10 tannins, 20 alkaloids, and 13 terpenoids. The result of clustering and PCA analyses showed that there was a great difference in metabolites between SZS at three growth stages. Differential metabolites in three comparison groups (T1 vs. T2, T2 vs. T3, and T1 vs. T3) were 195, 104, and 96, respectively. There were 29 common differential metabolites among the three different growth stages of SZS. The contents of important active ingredients (flavonoids and terpenoids) gradually increased during the T1, T2, and T3 stages, indicating that SZS harvested during T3 period was suitable for medicinal use. All the differential metabolites screened were enriched in 11 metabolic pathways, including glycerolipid metabolism, glycerophospholipid metabolism, phenylalanine metabolism, and phenylpropanoid biosynthesis pathway. Conclusions This study provides a more comprehensive understanding of the dynamic changes in the metabolic profile of SZS, laying a foundation for subsequent development and utilization.